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Tumor necrosis factor-alpha in the nucleus pulposus mediates radicular pain, but not increase of inflammatory peptide, associated with nerve damage in mice.
Spine (Phila Pa 1976). 2008 Aug 01; 33(17):1836-42.S

Abstract

STUDY DESIGN

Changes in behavior and the immunohistochemistry of dorsal root ganglion (DRG) neurons were examined using a mouse model of radicular pain.

OBJECTIVE

To examine the effects of TNF-alpha in the nucleus pulposus (NP) on nerve roots.

SUMMARY OF BACKGROUND DATA

Radicular pain is induced by mechanical compression and inflammation of nerve roots. Many authors have reported that following disc herniation, producing TNF-alpha plays a major role in neuropathic pain. Their findings suggest that TNF-alpha contained in the NP is significant in the development of pain and nerve root degeneration, but it has not been clearly demonstrated.

METHODS

Wild-type NPs or TNF-KO NPs, which were harvested from C57BL/6 mice (wild-type NP) or TNF-knock-out mice (TNF-KO NP), were applied to the left sciatic nerves of 30 wild-type mice, and the nerves were pinched. Production of hind paw mechanical allodynia, activating transcription factor 3, and calcitonin gene- related peptide (CGRP) were assessed.

RESULTS

Animals receiving a NP application demonstrated significant mechanical allodynia compared to the pinch-only and the control groups. The degree of mechanical allodynia was greater in the wild-type than in the TNF-KO group. The number of activating transcription factor 3 immunoreactive neurons was significantly higher in the wild-type than in the TNF-KO group. The number of CGRP-immunoreactive neurons was higher in the wild-type and TNF-KO than in the control groups. However, no significant difference in activity was observed between both CGRP positive groups.

CONCLUSION

In this study TNF-alpha contained in the NP was important for the production of radicular pain accompanied by long-lasting degeneration of DRG neurons. However, other cytokines in the NP and nerve compression may also play important roles in pain transmission. In this model system, TNF-alpha in the NP appears to mediate pain, but not cause an increase in CGRP in the DRG neurons.

Authors+Show Affiliations

Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. masaomiym@aol.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

18670336

Citation

Yamashita, Masaomi, et al. "Tumor Necrosis Factor-alpha in the Nucleus Pulposus Mediates Radicular Pain, but Not Increase of Inflammatory Peptide, Associated With Nerve Damage in Mice." Spine, vol. 33, no. 17, 2008, pp. 1836-42.
Yamashita M, Ohtori S, Koshi T, et al. Tumor necrosis factor-alpha in the nucleus pulposus mediates radicular pain, but not increase of inflammatory peptide, associated with nerve damage in mice. Spine (Phila Pa 1976). 2008;33(17):1836-42.
Yamashita, M., Ohtori, S., Koshi, T., Inoue, G., Yamauchi, K., Suzuki, M., & Takahashi, K. (2008). Tumor necrosis factor-alpha in the nucleus pulposus mediates radicular pain, but not increase of inflammatory peptide, associated with nerve damage in mice. Spine, 33(17), 1836-42. https://doi.org/10.1097/BRS.0b013e31817bab2a
Yamashita M, et al. Tumor Necrosis Factor-alpha in the Nucleus Pulposus Mediates Radicular Pain, but Not Increase of Inflammatory Peptide, Associated With Nerve Damage in Mice. Spine (Phila Pa 1976). 2008 Aug 1;33(17):1836-42. PubMed PMID: 18670336.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tumor necrosis factor-alpha in the nucleus pulposus mediates radicular pain, but not increase of inflammatory peptide, associated with nerve damage in mice. AU - Yamashita,Masaomi, AU - Ohtori,Seiji, AU - Koshi,Takana, AU - Inoue,Gen, AU - Yamauchi,Kazuyo, AU - Suzuki,Munetaka, AU - Takahashi,Kazuhisa, PY - 2008/8/2/pubmed PY - 2009/1/29/medline PY - 2008/8/2/entrez SP - 1836 EP - 42 JF - Spine JO - Spine (Phila Pa 1976) VL - 33 IS - 17 N2 - STUDY DESIGN: Changes in behavior and the immunohistochemistry of dorsal root ganglion (DRG) neurons were examined using a mouse model of radicular pain. OBJECTIVE: To examine the effects of TNF-alpha in the nucleus pulposus (NP) on nerve roots. SUMMARY OF BACKGROUND DATA: Radicular pain is induced by mechanical compression and inflammation of nerve roots. Many authors have reported that following disc herniation, producing TNF-alpha plays a major role in neuropathic pain. Their findings suggest that TNF-alpha contained in the NP is significant in the development of pain and nerve root degeneration, but it has not been clearly demonstrated. METHODS: Wild-type NPs or TNF-KO NPs, which were harvested from C57BL/6 mice (wild-type NP) or TNF-knock-out mice (TNF-KO NP), were applied to the left sciatic nerves of 30 wild-type mice, and the nerves were pinched. Production of hind paw mechanical allodynia, activating transcription factor 3, and calcitonin gene- related peptide (CGRP) were assessed. RESULTS: Animals receiving a NP application demonstrated significant mechanical allodynia compared to the pinch-only and the control groups. The degree of mechanical allodynia was greater in the wild-type than in the TNF-KO group. The number of activating transcription factor 3 immunoreactive neurons was significantly higher in the wild-type than in the TNF-KO group. The number of CGRP-immunoreactive neurons was higher in the wild-type and TNF-KO than in the control groups. However, no significant difference in activity was observed between both CGRP positive groups. CONCLUSION: In this study TNF-alpha contained in the NP was important for the production of radicular pain accompanied by long-lasting degeneration of DRG neurons. However, other cytokines in the NP and nerve compression may also play important roles in pain transmission. In this model system, TNF-alpha in the NP appears to mediate pain, but not cause an increase in CGRP in the DRG neurons. SN - 1528-1159 UR - https://www.unboundmedicine.com/medline/citation/18670336/Tumor_necrosis_factor_alpha_in_the_nucleus_pulposus_mediates_radicular_pain_but_not_increase_of_inflammatory_peptide_associated_with_nerve_damage_in_mice_ L2 - https://doi.org/10.1097/BRS.0b013e31817bab2a DB - PRIME DP - Unbound Medicine ER -